Overview
- Patients with breast cancer in an early, potentially curable stage (without metastases) who received preoperative (neoadjuvant) therapy are eligible to participate in the COGNITION-GUIDE study.
- The tumor tissue was previously analyzed molecularly in the COGNITION study using the latest methods to determine whether certain biomarkers are present.
- The goal of COGNITION-GUIDE is to determine whether targeted therapies can reduce the risk of breast cancer recurrence in patients with a high risk of relapse.
- To this end, the study team is evaluating 6 different targeted agents, each of which is tailored to a specific biological characteristic (biomarkers) of the tumor.
Study status: The study is currently enrolling patients (recruitment open).
Breast cancer develops due to changes in the DNA of cells in the mammary gland. These mutated cancer cells then have different characteristics than healthy cells.
Some of these molecular changes can be specifically targeted for treatment. Drugs that target these changes are called targeted cancer drugs. These drugs preferentially target altered cancer cells and largely spare the body’s healthy cells.
In breast cancer, as well as in other types of cancer, the patterns of molecular changes can vary significantly from person to person and even from one tumor tissue sample to another. For this reason, different patients often receive different active ingredients in targeted therapies—even if their clinical situations appear very similar at first glance.
In the COGNITION-GUIDE study, experts are examining patients with early-stage breast cancer whose tumors responded poorly to neoadjuvant therapy prior to surgery. These patients often have an increased risk of the tumor returning. The goal is to determine whether targeted therapies can reduce the risk of recurrence in these patients.
- For detailed information on the specific objectives of the COGNITION-GUIDE study, please refer to the section “What is the goal of the COGNITION-GUIDE study?”.
The COGNITION-GUIDE study treats patients with breast cancer:
- Whose disease is in an early, potentially curable stage (there is no metastasis).
- Who, due to an increased risk of recurrence, received neoadjuvant therapy prior to surgery.
- In whom this treatment has had only limited or no effect—meaning that residual tumor cells were detected during surgery. Analysis of these cells may provide clues regarding appropriate targeted therapies.
To learn about the other eligibility criteria for patients wishing to participate in the study, please see the section “Who is the study suitable for?”.
COGNITION-GUIDE is the English acronym for: “Genomics-guided targeted post-neoadjuvant therapy in patients with early breast cancer – Module Therapy.”
In other words:
Patients with breast cancer at an early, potentially curable stage receive targeted therapy tailored to the molecular alterations in their tumor. This drug treatment takes place following the completion of standard therapy after surgery. This is also referred to as post-neoadjuvant therapy.
Objective of the COGNITION-GUIDE Study
- The goal is to offer targeted therapy to patients with early-stage breast cancer who are at increased risk of recurrence. This therapy is precisely tailored to the biological characteristics of the tumor cells. A total of 6 different study drugs are included among the recommended medications.
- Targeted therapy, used in addition to standard treatment, is intended to further reduce the risk of recurrence and the risk of metastasis. To assess this, the doctors are monitoring how many of the participants remain free of breast cancer following completion of therapy.
Other objectives include determining how well patients with early-stage breast cancer tolerate targeted cancer drugs as well as assessing the participants’ quality of life.
Patients may be eligible for participation in the COGNITION-GUIDE study if both of the following criteria are met:
- Their breast cancer is at an early stage and has not metastasized.
- Residual tumor is still detectable after standard neoadjuvant therapy.
The tumor should also have one of the following characteristics:
- The breast cancer is HER2-positive: “HER2-positive” means that large amounts of the HER2 protein can be detected on the surface of the breast cancer cells. HER2 transmits growth signals to the cancer cells.
- The breast cancer is “triple-negative”: “Triple-negative” means that the breast cancer cells lack binding sites for the female sex hormones estrogen and progesterone (i.e., they are hormone receptor-negative) and do not express HER2 on their surface.
- The breast cancer is hormone receptor-positive but HER2-negative: This means that the breast cancer cells have binding sites for the female sex hormones estrogen and progesterone, and do not have large amounts of HER2 protein on their surface.
In addition, all of the following criteria must be met:
- The patient is at least 18 years old.
- Preoperative (neoadjuvant) therapy, the surgery itself, and standard postoperative therapy (such as radiation therapy) have been completed.
- The patient’s general health is good. This means the patient can manage daily life without major limitations.
- The patient has signed a consent form.
Patients cannot participate in the study if any of the following criteria apply:
- The patient has had another cancer within the last five years. Exceptions to this include certain cancers that were detected early and successfully treated. Examples include basal cell carcinoma, a precancerous stage of cervical cancer, or an early precancerous stage of breast cancer (DCIS).
- The patient has a serious comorbid condition or impairment that precludes participation in the study.
- The patient is currently participating in another clinical trial or has done so within the last 30 days.
COGNITION-GUIDE is structured as follows:
- Multicenter Study: Patients can participate at several NCT study sites in Germany. Find more information in the section „Where is the study being conducted?”.
- Open-Label Phase II Trial: All participants know which treatment is being administered. Experts refer to this as “open-label.” A Phase II trial evaluates how well the treatment works and how well it is tolerated.
- 7-Arm Intervention Study: The COGNITION-GUIDE study is testing 6 different targeted cancer drugs. By administering these drugs, the study physicians are intervening in the course of the disease (intervention). In the 7th group, patients who receive only standard therapy and no additional treatment are observed for comparison.
(1) Initial Consultation and Informed Consent
During the initial consultation, the patient learns about the study’s objectives, the potential benefits of participation, and any risks involved. This also serves as an opportunity to ask questions about the procedure of the study. If patients decide to participate after this meeting, they must submit a written informed consent form.
(2) Selection of Participants
The selection and grouping of patients generally takes place within the framework of the molecular tumor board of the COGNITION Diagnostics Study based on the results of the molecular analyses. You can read about the eligibility criteria for participants in the section “Who is the study suitable for?”.
(3) Assignment to Treatment Groups
Patients are assigned to different groups according to their respective treatment recommendations.
Participants are divided into 6 groups, each receiving different active substances tailored to the biological characteristics of their tumor (targeted cancer drugs). Which of the 6 groups a person is assigned to depends on which biomarkers were detected in their tumor tissue.
The following targeted agents are being studied in the 6 treatment groups:
- Group 1: Atezolizumab
- Group 2: Inavolisib
- Group 3: Ipatasertib
- Group 4: Olaparib
- Group 5: Sacituzumab govitecan
- Group 6: Trastuzumab/Pertuzumab
Group 7 (observation group) serves as the control group. In this group, the study physicians assign patients
- for whom it was not possible to determine the exact genetic characteristics of the tumor OR
- if no biomarkers matching the active pharmaceutical ingredients could be detected in the tumor tissue.
(4) Treatment Phase
After patients have completed standard breast cancer therapy (exception: endocrine therapy), they are enrolled in the COGNITION-GUIDE study 1 to 3 months later.
Treatment with the study drug lasts approximately 12 months for each patient. During this time, participants must visit the study center regularly for treatment and/or follow-up visits. The frequency of these visits depends on the specific study drug.
Patients in the observation group are asked to come to the study center for follow-up examinations every 3 months during the 12-month period.
(5) Follow-up
Follow-up begins after completion of targeted therapy in the treatment groups or after the first year in the observation group.
This corresponds to breast cancer follow-up care, which takes place as part of routine clinical practice. During a consultation, the study team assesses the patient’s current health status and the medications being taken. The breast is then examined, and an ultrasound (sonography) and mammography may be performed.
If follow-up care does not take place at the study center, the treating physician will forward the results to the study team.
For the COGNITION-GUIDE study, data is collected at the following time points:
- every 3 months for the first 3 years,
- thereafter every 6 months
The average follow-up period ends for all participants at the conclusion of the study, which is approximately 7.5 years after the last patient’s breast cancer surgery.
If the cancer comes back during follow-up or at any time later, the participant is asked to contact the study team.
The data collected during the follow-up phase will be scientifically analyzed. It will be used to assess the efficacy and safety of the treatment over a longer period of time and to evaluate the study’s objectives.
These are the potential benefits of participating in the COGNITION-GUIDE study:
- Patients can benefit from modern precision oncology approaches and receive treatment that is tailored (personalized) to their specific cancer biomarkers.
- Targeted therapy could improve a patient’s chances of recovery and reduce the risk of recurrence and metastasis.
- The study results may help improve the treatment of patients with early-stage breast cancer in the future. Since the effectiveness of the study drugs has not yet been proven, it is possible that the patient will not derive any direct benefit from participating in the study.
However, participating in the COGNITION-GUIDE study may also have disadvantages:
- Treatment with one of the active pharmaceutical ingredients may cause side effects or discomfort. The treating study physician will discuss potential risks with study participants during the initial consultation.
Where is the study being conducted?
Patients can participate in the COGNITION-GUIDE study through the corresponding NCT sites.
The addresses and contact information for the study centers are as follows:
Heidelberg
National Center for Tumor Diseases (NCT) Heidelberg
Prof. Dr. Andreas Schneeweiss
Phone: 06221 56 5959
E-mail: Patientenzentrum2.NCT-at-med.uni-heidelberg.de
Augsburg
Augsburg University Hospital
Prof. Dr. Nina Ditsch
Phone: 0821 400 2208
E-mail: studien.gyn-at-uk-augsburg.de
Berlin
Charité – Berlin University Medical Center, Department of Gynecology, including the Breast Center CCM/CBF
Prof. Dr. Jens-Uwe Blohmer
Phone: 030 450 664485
E-mail: brustzentrum-studienzentrum-at-charite.de
Dresden
Dresden University of Technology, Carl Gustav Carus Medical Faculty
Prof. Pauline Wimberger, M.D.
Phone: 0351 458 4223
E-mail: studiensekretariat.gyn-at-ukdd.de
Erlangen
Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen University Hospital, Department of Obstetrics and Gynecology
Prof. Peter Fasching, M.D.
Phone: 0941 782 7512
E-mail: FHK-Studienzentrum-at-csj.de
Cologne
Department of Gynecology and Gynecologic Oncology
Dr. Christian Maurer, M.D.; Tel.: 0221 478 89213
E-mail: Frauenklinik-Studienzentrale-at-uk-koeln.de
Tübingen
University Hospital of Tübingen
Prof. Dr. Andreas Hartkopf
E-mail: studienzentrale.fr-at-med.uni-tuebingen.de
Ulm
University Hospital Ulm, Department of Obstetrics and Gynecology
Prof. Dr. Wolfgang Janni
Phone: 0731 500 58529
E-mail: studienzentrale.ufk-at-uniklink-ulm.de
Würzburg
Department of Obstetrics and Gynecology and Outpatient Clinic of the University Hospital
Prof. Achim Wöckel, M.D.
E-mail: Studien_FK-at-ukw.de
What costs will participants incur?
Participation in the study is free of charge for patients. However, you will not receive any compensation for your time. Travel expenses are not reimbursed as part of the study.
If you have any questions about the study’s funding, you can ask the study team, for example during the initial consultation.
How many participants will the study accept? Are there still places available?
The COGNITION-GUIDE study will enroll a total of 240 patients. You can find out whether participation is possible by contacting the respective study centers.
Enrollment in the COGNITION-GUIDE study takes place directly at the participating study center. If the study center is not currently recruiting for COGNITION-GUIDE, you may be referred to the nearest actively recruiting study center.
Was the patient’s cancer tissue typified as part of the MOMENTUM study?
If so, treating physicians or patients can mail existing documents and information to an NCT study center near the patient’s place of residence. The required documents for enrollment include the:
- most recent doctor’s letter
- results from the tissue examination and imaging studies
- surgical report
- tumor board recommendation
- patient’s contact information (including a phone number)
- referral form
The COGNITION-GUIDE study is supported by representatives from the following patient organizations:
- Mamma Mia! – The Breast Cancer Magazine
- Breast Cancer Germany e.V.
- PATH Foundation – Patients’ Tumor Bank of Hope
Those interested can find more information about COGNITION-GUIDE on the NCT Heidelberg study website and at the following links:
- Flyer on CATCH and COGNITION (PDF | German)
- Cancer guide “Mamma Mia!” – Precision Oncology (PDF | German)
Scientific Publications (Selection)
Pixberg, C., Zapatka, M., Hlevniak, M. et al. COGNITION: a prospective precision oncology trial for patients with early breast cancer at high risk following neoadjuvant chemotherapy. ESMO Open 7, 100637 (2022). https://doi.org/10.1016/j.esmoop.2022.100637
Pixberg C, Maurer C, Smetanay K, Straßl L, Hlevnjak M, Zapatka M, Wagner CV, Yazdanparast H, Kurzawa J, Erben V, Schneeweiss A., et al. COGNITION-GUIDE - Genomics-Guided Targeted Post-Neoadjuvant Therapy in Patients with Early Breast Cancer: Study Design of a Multicenter, Open-Label, Umbrella Phase II Study. Geburtshilfe Frauenheilkd. April 10, 2025;85(6):611-619. doi: 10.1055/a-2557-1876
This study description was prepared by authors from the Cancer Information Service, under the direction of Dr. S. Weg-Remers, based on the study documentation.